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Thorax 2004;59:687-693
© 2004 BMJ Publishing Group Ltd & British Thoracic Society


INTERSTITIAL LUNG DISEASE

Expression of glucocorticoid receptors {alpha} and ß in steroid sensitive and steroid insensitive interstitial lung diseases

L Pujols1, A Xaubet1,2, J Ramírez1,3, J Mullol1,4, J Roca-Ferrer1, A Torrego1,2, J A Cidlowski5, C Picado1,2

1 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
2 Servei de Pneumologia i Al.lèrgia Respiratòria, Institut Clínic de Pneumologia i Cirurgia Toràcica, Hospital Clínic, Departament de Medicina, Universitat de Barcelona, Barcelona, Spain
3 Servei d’Anatomia Patològica, Hospital Clínic, Barcelona, Spain
4 Servei d’Otorinolaringologia, Hospital Clínic, Barcelona, Spain
5 Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA

Correspondence to:
Correspondence to:
Dr C Picado
Servei de Pneumologia, ICPCT, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain; cpicado{at}ub.edu

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors {alpha} (GR{alpha}) and ß (GRß). A study was undertaken to assess GR{alpha} and GRß expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)).

Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GR{alpha} and GRß expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25–75th percentile.

Results: GR{alpha} mRNA expression (105 cDNA copies/µg total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.8–14.9; n = 11) than in patients with IPF (4.4; 3.2–6.6; n = 19; p<0.001). GRß expression was at least 1000 times lower than that of GR{alpha} and did not differ between the three groups. A negative correlation was found between GR{alpha} mRNA levels and the fibrotic pathology score of the tissue (r = –0.484, p<0.01) and a positive correlation was found between GR{alpha} mRNA levels and improvement in forced vital capacity (r = 0.633; p<0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF.

Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GR{alpha}.


Abbreviations: COP, cryptogenic organising pneumonia; IPF, idiopathic pulmonary fibrosis; GR, glucocorticoid receptor; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; TLCO, carbon monoxide transfer factor

Keywords: glucocorticoids; glucocorticoid receptors; idiopathic pulmonary fibrosis; sarcoidosis; cryptogenic organising pneumonia




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